Exposure to a more diverse range of microbes explains why children raised on a farm have a lower risk of asthma, researchers reported.

Action Points

Note that in this study, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than children living in the same areas but not raised on farms.

Point out that there is hope that this and other new conceptual breakthroughs may lead to novel preventive strategies such as vaccines for atopy and asthma.

Children growing up on farms have a much lower risk of asthma than others, but it's not all that fresh air and exercise that turns the trick.

Instead, it's exposure to a larger range of bacteria and fungi in the barnyard.

That's the conclusion of investigators who reported in the Feb. 24 issue of the New England Journal of Medicine on two large European cross-sectional studies that looked at asthma and atopy in more than 16,500 elementary school children.

Exposure to microbes "explains a substantial fraction of the inverse relation between asthma and growing up on a farm," according to Markus Ege, MD, of the University of Munich, and colleagues.

If specific microbes can be found that are involved in the protective effect, Ege said in a statement, it might be possible to develop a vaccine against asthma.

"We have a long way to go before we can present new preventive measures, but at least we now have candidates for the development of a vaccine," he said.

The finding "offers hope" for new preventive strategies but several questions remain, argued James Gern, MD, of the University of Wisconsin School of Medicine and Public Health in Madison, Wis.

Among other things, Gern noted in an accompanying editorial, the researchers measured exposure, but didn't look at what microbes actually colonize children.

Also, he said, the picture of microbial diversity is still painted in only broad strokes, and many details remain imprecise.

Other experts cautioned that there are a host of other differences between farm and city life that were not measured in the study, so it is premature to conclude that germs are even related to a reduction in asthma risk, let alone cause it.

Said Harley Rotbart, MD, of the University of Colorado School of Medicine in Denver, the "diversity of nonmicrobial differences between farm and nonfarm life makes studies like this very difficult to interpret."

Such things as animal dander, soil, and pesticides on the farm and soot, car exhaust, and asbestos in the city could also play a role, Rotbart argued in an e-mail to MedPage Today/ABC News.

"Until the specific causes or triggers of atopy and asthma are established, it is premature to broadly conclude that germ exposures are related, much less causal," Rotbart said.

The two studies -- dubbed PARSIFAL and GABRIELA -- replicated previous research showing that the incidence of asthma and atopy is lower among children raised on a family farm.

Specifically, compared with children who did not live on a farm:

Odds ratios for allergy were 0.49 in PARSIFAL and 0.76 in GABRIELA and both were significant at P<0.001.

Odds ratios for atopy were 0.24 in PARSIFAL and 0.51 in GABRIELA, and again both were significant at P<0.001.

Both studies investigated indoor dust exposure for a randomly selected subset of the children, using different methods.

In PARSIFAL, the investigators used single-strand conformation polymorphism analyses, in which known microbes produce recognizable bands on a gel. In GABRIELA, they employed traditional culture techniques.

Analysis showed that diversity of exposure was inversely related to the risk of asthma, Ege and colleagues reported.

Indeed, they found, for every additional 10 bands seen in the PARSIFAL study, the risk of asthma fell by 38% (OR 0.62, 95% CI 0.44 to 0.89).

Similarly, for each increase of one taxon in GABRIELA, the risk of asthma fell by 14% (OR 0.86, 95% CI 0.75 to 0.99).

On the other hand, microbial diversity had no significant impact on the risk of atopy, they reported.

The investigators reported that they identified several types of microbes that might be responsible for the reduction in asthma risk, including members of the fungal taxon eurotium and a variety of bacterial species, including Listeria monocytogenes, bacillus species, and corynebacterium species.

The mechanisms involved remain unclear, Ege and colleagues noted.

One possibility is that some combination of microbes stimulates the innate immune system and prevents it from entering a pro-asthma state, they argued.

It is also possible that exposure to many different microbes makes it harder for those that can induce asthma to become dominant in the lower respiratory tract, they noted.

In fact, Wesley Burks, MD, of Duke University Medical Center, said the results of the study "strongly support" the so-called hygiene hypothesis but are unlikely to lead to immediate changes.

"We need to understand better what specific part of this farm exposure is causing the difference in asthma," he said in an e-mail to MedPage Today/ABC News. "Then you can begin to treat everyone with that variable."

Clifford Bassett, MD, of the New York University School of Medicine, said the current hygiene theory -- which he called the "eat dirt hypothesis" -- gets additional support from the study.

In other words, he said in an e-mail to MedPage Today/ABC News, germs help in the maturation of a child's immune system and offer protection against asthma and related allergic disease.

The next challenge, Ege and colleagues concluded, is to identify the microbes involved with enough precision to allow tests of the two models.

This article was developed in collaboration with ABC News.

The study was supported by the Deutsche Forschungsgemeinschaft and the European Commission.

Ege did not report any financial links with industry, but his institution is planning a patent on asthma protective bacteria.

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